Estrogenic compounds and animal growth promoters



United States Patent OfiFice 3,373,028 ESTROGENIC COMPOUNDS AND ANIMALGROWTH PROMOTERS Edward B. Hodge, Phil H. Hidy, and Herbert L.Wehrmeister, Terre Haute, Ind., assignors to Commercial SolventsCorporation, a corporation of Maryland No Drawing. Continuation-impartof application Ser. No. 561,392, June 29, 1966. This application Mar. 3,1967, Ser. No. 620,262

Claims. (Cl. 99-2) ABSTRACT OF THE DISCLOSURE This application is acontinuation-in-part of application Ser. No. 561,392, filed June 29,1966, now abandoned.

The present invention relates to new carboxy-containing compounds and anobject of the present invention is to provide compounds which exhibitestrogenic acitivity or aid in increasing the rate of growth in meatproducing animals, e.g. cattle, lamb and swine.

A conventional formula for the compounds of the present invention is:

wherein A is CH CH or -CH=CH; B is C=O, CHOH or CH with the proviso thatA is -CH -CH when B is CH R is hydrogen, substituted or unsubstitutedalkyl, e.g. lower alkyl such as methyl, ethyl, heXyl, etc.; acyl, e.g.lower saturated acyclic acyl radicals such as acetyl; or aralkyl, e.g.benzyl; and one of X andY is CO H, with the other of X and Y beinghydrogen.

The compounds can be administered to animals by any suitable methodincluding oral and parenteral administrations. For example, the compoundcan be blended with ordinary feed containing nutritional values in anamount sufiicient to produce the desired rate of growth and can thus befed directly to the animals, or the compound can be suspended in asuitable injection suspension medium 3,373,628 Patented Mar. 12, 1968such as peanut oil and infected parenterally. The amount of compound fedto an animal, of course, varies depending upon the animal, desired rateof growth and the like.

When the new compounds are to be administered in feeds, an animal feedcomposition may be prepared containing the usual nutritionally-balancedquantities of carbohydrates, proteins, vitamins and minerals, togetherwith the compounds of the present invention. Some of these usual dietaryelements are grains, such as ground grain and grain by-products; animalprotein substances, such as those found in fish meal and meat scraps,vegetable proteins like soybean oil meal or peanut oil meal;vitaminaceous materials, e.g. vitamin A and D mixtures; riboflavinsupplements and other vitamin B complex members; and bone meal andlimestone to provide minerals. A type of conventional feed material foruse with cattle includes alfalfa hay and ground corn cobs together withsupplementary vitaminaceous substances if desired.

The carboxy compounds of the present invention are produced bycarboxylation using CO of the compound:

hereinafter referred to as the fermentation estrogenic substance(F.E.S.). The alkyl ethersof F.E.S. are described in US. Patent3,239,342 and compounds where R; is benzyl are described in copendingapplication Ser. No. 532,113, filed Mar. 7, 1966, now abandoned, andapplication Ser. No. 620,259, filed Mar. 3, 1967. U3. Patents 3,239,354,3,239,347 and 3,239,356 for example, describe F.E.S. compounds where Ais -CH -CH and R is acyl or a combination of alkyl and acyl. TetrahydroF.E.S. and deoxy F.E.S. where E is, respectively, CHOH and CH aredescribed in US. Patents 3,239,345 and 3,239,341. r

The following examples are oifered to illustrate this invention;however, the invention is not limited to the specific materials,amounts, and procedures set forth.

Example I Example II The product of 'Example I is acylated with aceticanhydride by the process described in US. Patent 3,239,347 to produce2,4-diacety1-5-carboxy-F.E.S.

Example III The 2-methyl ether.0f F.E.S., deoxy F.E.S. and tetrahydroF.E.S. are carboxylated according to the process of Example I to producethe corresponding S-carboxy F.E.S. compound.

3 Example IV The 4-benzyl ether of F.E.S. is carboxylated according tothe process of Example I to produce the S-carboxy- 4-benzyl ether ofExample V Six head of cattle are fed a daily ration including a mixtureof alfalfa hay and g ound corn cobs containing from 1 to 20 ounces ofS-carboxy RES. per hundred pounds of ration to increase the rate ofgrowth of the cattle.

Example VI Six head of cattle are fed a daily ration including a mixtureof alfalfa hay and ground corn cobs containing from 1 to 20 ounces ofthe S-carboxy-Z-benzyl ether of F.E.S. per hundred pounds of ration toincrease the rate of growth of the cattle.

Example VII Six head of cattle are fed a daily ration including amixture of alfalfa hay and ground corn cobs containing from 1 to 20ounces of 5-carboxy-2-methyl ether of dihydro F.E.S. per hundred poundsof ration to increase the rate of growth of the cattle.

Example VIII Six head of cattle are fed a daily ration including amixture of alfalfa hay and ground corn cobs containing from 1 to 20ounces of 5-carboxy-deoxy RES. per hundred pounds of ration to increasethe rate of growth of the cattle.

The following are specific examples of animal feed compositions of thisinvention useful for increasing the rate of growth and feed eificiencyof young animals to market weight.

Example IX For young beef cattle, i.e., calves to yearlings running totwo year olds, each animal is given 5 to 20 milligrams per day of thecompound produced in Example I intimately admixed in about 18 to 22pounds per head per day of a complete pelleted ration for about 180days. The complete pelleted ration includes in addition to the com-Note.Milo or corn, for example, can be substituted for the barley.

The compound of Example I is admixed with the above ingredients in astationary blender or a feed mix truck in the following amounts in gramsper ton to provide an appropriate complete pelleted feed with dosagelevels ranging from 5 to 90 milligrams per head per day.

Grams/ton: Mg/head/day .5 5 1.0 2.0 4.0 8.0 80

These gram amounts are premixed with, for example, 10 pounds of soybeanhulls prior to admixture with the other ingredients.

Example X For young swine, i.e., six week old pigs to about pound pigs,each animal is given 5 to 2 milligrams per day of the compound ofExample II intimately admixed in about 1 /2 to 5 /2 pounds per head perday of a grower ration until it reaches a weight of about 100 pounds.When the swine weigh between 90 and pounds the feed is changed to onewhereby each animal is given 20 to 50 milligrams per day of the compoundof Example II intimately admixed in about 5 /2 to 10 pounds per head perday of a finisher ration until it reaches market weight of about 220pounds. The grower and finisher ration include in addition to thecompound of Example II the following:

Grower, Finisher, percent percent Ground Yellow Corn 77 86.7 SoybeanMeal (44% protein). 16 6.5 Meat and Bone Scraps (50% prot 2. 5 2. 5Dehydrate Alfalfa Meal (17%) 2. 5 2. 5 Steamed Bone Meal 0. 5 0. 5Ground Limestone 0. 5 0.3 Iodlzed Salt 0. 5 0. 5 Vitamin, Antibiotic andTrace Mineral Prernix 0. 5 0. 5

The compound of Example II is admixed with the above ingredients in ablender in the following amounts in milligrams per pound to provide anappropriate feed with dosage levels ranging from 6 to 96 milligrams perhead per day.

Mg/ pound Mg/ head/ day 2 6 4 12 8 24 16 48 32 96 Example XI For 4 to 10month old lambs weighing 50 to 70 pounds, each animal is given 1 tomilligrams per day of the compound of Example IV, intimately admixed inabout 3 to 6 pounds per head per day of a complete ration for 30 to 90days. The complete ration includes in addition to the compound ofExample IV the following:

The compound of Example IV is admixed with the above ingredients in ablender in the following amounts in milligrams per pound to provide anappropriate complete feed with dosage levels ranging from 1 to 15milligrams per head per day.

Mg/ pound: Mg/head/day .5 2

Example XII For broilers, i.e., day old to four week old chicks, agrower feed is prepared for feeding to the chicks for the first fourweeks and a finisher feed is prepared for feeding the four Week oldchicks for the last five Weeks until they reach market weight of two anda half to three pounds dressed. For each pound of weight gain, thechicks eat about 1.5 to 2 pounds of feed. Thus they eat about 1.5 poundsof feed during the first four weeks and about five pounds of feed duringthe next five weeks. During the course of this feeding schedule, eachbird should receive a total of about 12 to 36 milligrams of the compoundof Example IV in the grower and finisher feed each of which includes inaddition to the compound of Example IV the following:

Grower Finisher (1115.) (lbs) Ground Yellow Corn 1,000 1, 200 SoybeanMeal (44% Protein) 700 500 Fish Meal (60% Piote1n)- 100 80 Altai 50 50Meat and Bone Scraps". 30 Animal Fat 80 80 Dicalcium Phosphate 35 40Iodized Salt 10 10 Limestone l5 Premix Vitamins Trace Minerals an Abiotics 10 It is claimed: 1.

' o-on-(om). X

B R-O where A is a radical selected from the group consisting of -CH CHand -CH=CH-; R is selected from the group consisting of hydrogen, loweralkyl, benzyl and lower saturated acyclic acyl, one of X and Y is -CO Ham the other is hydrogen; and B is a radical selected from the groupconsisting of C=O, CHOH and CH with the proviso that A is -CH CH when Bis CH 2. The compound of claim 1 wherein X is hydrogen, Y is CO H and Bis C=O.

3. The compound of claim 1 wherein X is -CO H, Y is hydrogen and B isC=O.

4. The compound of claim 1 wherein B is C=O.

5. The compound of claim 2 wherein R is lower alkyl.

6. The compound of claim 2 wherein R is hydrogen.

7. The compound of claim 2 wherein R is benzyl.

8. The compound of claim 3 wherein R is lower alkyl.

9. The compound of claim 3 wherein. R is hydrogen.

10. An animal feed comprising a nutritional diluent and growth promotingamounts of the compound of claim 1.

No references cited.

A. LOUIS MONACELL, Primary Examiner.

H. H. KLARE, Assistant Examiner.

